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J. Cell Biol.,
Volume 141, Number 2, April 20, 1998 527-538
1A Integrin Functions by
Tyrosine Residues in the 1 Cytoplasmic Domain
* Departments of Medicine and Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI 53706; and Department of Experimental Pathology, Lund University, 22185 Lund, Sweden
1A integrin subunits with point mutations
of the cytoplasmic domain were expressed in fibroblasts derived from 1-null stem cells. 1A in which
one or both of the tyrosines of the two NPXY motifs
(Y783, Y795) were changed to phenylalanines formed
active 
51 and 61 integrins that mediated cell adhesion and supported assembly of fibronectin. Mutation
of the proline in either motif (P781, P793) to an alanine
or of a threonine in the inter-motif sequence (T788) to
a proline resulted in poorly expressed, inactive 1A.
Y783,795F cells developed numerous fine focal contacts and exhibited motility on a surface. When compared with cells expressing wild-type 1A or 1A with
the D759A activating mutation of a conserved membrane-proximal aspartate, Y783,795F cells had impaired ability to transverse filters in chemotaxis assays.
Analysis of cells expressing 1A with single Tyr to Phe
substitutions indicated that both Y783 and Y795 are
important for directed migration. Actin-containing microfilaments of Y783,795F cells were shorter and more
peripheral than microfilaments of cells expressing wild-type 1A. These results indicate that change of the
phenol side chains in the NPXY motifs to phenyl
groups (which cannot be phosphorylated) has major effects on the organization of focal contacts and cytoskeleton and on directed cell motility.
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